Safety and Efficacy of Inpatient Diabetes Management with Non-insulin Agents: an Overview of International Practices.

PURPOSE OF REVIEW: The field of inpatient diabetes has advanced significantly over the last 20 years, leading to the development of personalized treatment approaches. However, outdated guidelines still recommend the use of basal-bolus insulin therapy as the preferred treatment approach, and against the use of non-insulin anti-hyperglycemic agents. RECENT FINDINGS: Several observational and prospective randomized controlled studies have demonstrated that oral anti-hyperglycemic agents are widely used in the hospital, including studies of DPP-4 agents and GLP-1 agonists. With advances in the field of inpatient diabetes management, a paradigm shift has occurred, from an approach of recommending "basal-bolus regimens" for all patients to a more precision medicine option for hospitalized non-critically ill patients with type 2 diabetes.

Understanding the clinical implications of differences between glucose management indicator and glycated haemoglobin.

Laboratory measured glycated haemoglobin (HbA1c) is the gold standard for assessing glycaemic control in people with diabetes and correlates with their risk of long-term complications. The emergence of continuous glucose monitoring (CGM) has highlighted limitations of HbA1c testing. HbA1c can only be reviewed infrequently and can mask the risk of hypoglycaemia or extreme glucose fluctuations. While CGM provides insights in to the risk of hypoglycaemia as well as daily fluctuations of glucose, it can also be used to calculate an estimated HbA1c that has been used as a substitute for laboratory HbA1c. However, it is evident that estimated HbA1c and HbA1c values can differ widely. The glucose management indicator (GMI), calculated exclusively from CGM data, has been proposed. It uses the same scale (% or mmol/mol) as HbA1c, but is based on short-term average glucose values, rather than long-term glucose exposure. HbA1c and GMI values differ in up to 81% of individuals by more than ±0.1% and by more than ±0.3% in 51% of cases. Here, we review the factors that define these differences, such as the time period being assessed, the variation in glycation rates and factors such as anaemia and haemoglobinopathies. Recognizing and understanding the factors that cause differences between HbA1c and GMI is an important clinical skill. In circumstances when HbA1c is elevated above GMI, further attempts at intensification of therapy based solely on the HbA1c value may increase the risk of hypoglycaemia. The observed difference between GMI and HbA1c also informs the important question about the predictive ability of GMI regarding long-term complications.

Titratable fixed-ratio combination of basal insulin plus a glucagon-like peptide-1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes.

Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon-like peptide-1 receptor agonist (GLP-1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real-world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta-analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head-to-head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP-1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP-1 RAs as an alternative treatment option.

Effectiveness of premixed insulin to achieve glycaemic control in type 2 diabetes: A retrospective UK cohort study.

AIM: To investigate the effectiveness of premixed insulin for achieving glycaemic outcomes in clinical practice in the UK. MATERIALS AND METHODS: Electronic medical record data from The Health Improvement Network database were captured for adults with type 2 diabetes (T2D) uncontrolled (HbA1c ≥9%) on two or more oral antihyperglycaemic drugs (OADs) initiating premixed insulin. Effectiveness of premixed insulin was assessed by the probability and incidence of achieving glycaemic outcomes (target HbA1c <7.5% [<58 mmol/mol] and a ≥1% or ≥2% HbA1c reduction) over 24 months. RESULTS: Data from 974 participants (mean age 62 years; 56% male; 52% obese or extremely obese; mean HbA1c 11.3% [100 mmol/mol]; hypertension 64%, dyslipidaemia 23% and nephropathy 21%) were analysed. The probability of achieving HbA1c <7.5% was highest during months 3-6 (18.2%), while the cumulative probability of achieving this target plateaued between months 15-24 (15.7%-16.0%). Incidence of achieving all glycaemic outcomes plateaued after 12 months and differed by baseline HbA1c, but not OAD use. Factors affecting some glycaemic outcomes included a body mass index >40 kg/m2 and co-morbidities including nephropathy and stroke. CONCLUSIONS: In people with uncontrolled T2D (HbA1c ≥9%), glycaemic outcome achievement on premixed insulin was low at 6 months with little additional clinical benefit beyond 12 months, suggesting a high unmet need for early, timely treatment changes with more effective, simpler therapies.

An association between liraglutide treatment and reduction in excessive daytime sleepiness in obese subjects with type 2 diabetes.

BACKGROUND: The main purpose of the present study is to evaluate whether treatment with long-acting human glucagon-like peptide-1 liraglutide was associated with an improvement of excessive daytime sleepiness (EDS) in obese subjects with type-2 diabetes. METHODS: This single-centre retrospective study included 158 obese (body mass index [BMI] ≥ 30 kg/m(2)) adult subjects with type-2 diabetes who were initiated with liraglutide treatment at least 3 months before study inclusion. Data of the Epworth Sleepiness Scale (ESS), anthropometric parameters, glucose-control and metabolic parameters were collected at liraglutide initiation (baseline) and at months 1 and 3 after liraglutide initiation. RESULTS: Significant reductions in ESS score were achieved at months 1 (-1.3 ± 2.8, p < 0.001) and 3 (-1.5 ± 3.0, p < 0.001) after liraglutide introduction. After 3 months of treatment with liraglutide, significant changes in body weight (p < 0.001), BMI (p < 0.001), waist (p < 0.001) and neck circumferences (p < 0.005), HbA1c (p < 0.001), mean blood glucose (p < 0.001), fasting plasma glucose (p < 0.001), triglycerides (p < 0.01) and total cholesterol (p < 0.001) were achieved. CONCLUSIONS: After 3 months of treatment with liraglutide a significant reduction in EDS was observed in obese subjects with type-2 diabetes. Besides this, significant changes in body weight and metabolic parameters of diabetes control were also accomplished. Further investigation is required to determine whether liraglutide could improve other abnormal sleep patterns and obstructive sleep apnoea.

Impact of Continuous Glucose Monitoring and its Glucometrics in Clinical Practice in Spain and Future Perspectives: A Narrative Review.

INTRODUCTION: Continuous glucose monitoring (CGM) devices allow for 24-h real-time measurement of interstitial glucose levels and have changed the interaction between people with diabetes and their health care providers. The large amount of data generated by CGM can be analyzed and evaluated using a set of standardized parameters, collectively named glucometrics. This review aims to provide a summary of the existing evidence on the use of glucometrics data and its impact on clinical practice based on published studies involving adults and children with type 1 diabetes (T1D) in Spain. METHODS: The PubMed and MEDES (Spanish Medical literature) databases were searched covering the years 2018-2022 and including clinical and observational studies, consensus guidelines, and meta-analyses on CGM and glucometrics conducted in Spain. RESULTS: A total of 16 observational studies were found on the use of CGM in Spain, which have shown that cases of severe hypoglycemia in children with T1D were greatly reduced after the introduction of CGM, resulting in a significant reduction in costs. Real-world data from Spain shows that CGM is associated with improved glycemic markers (increased time in range, reduced time below and above range, and glycemic variability), and that there is a relationship between glycemic variability and hypoglycemia. Also, CGM and analysis of glucometrics proved highly useful during the COVID-19 pandemic. New glucometrics, such as the glycemic risk index, or new mathematical approaches to the analysis of CGM-derived glucose data, such as "glucodensities," could help patients to achieve better glycemic control in the future. CONCLUSION: By using glucometrics in clinical practice, clinicians can better assess glycemic control and a patient's individual response to treatment.

Continuous glucose monitoring (CGM) devices are used to monitor glucose levels in real time over 24 h. This has changed the way people with diabetes and their health care providers interact. These devices produce a large amount of data that can be analyzed and evaluated using standardized parameters called glucometrics, which include the time a patient's glucose is in range, below range, and above range, and how much it varies over 24 h. Clinicians can use these data to better assess glycemic control and a patient's individual response to treatment. In this article, we summarize evidence from published studies involving adults and children with type 1 diabetes in Spain to look at how the use of these data has affected clinical practice. Studies have shown that cases of severe low blood glucose in children with diabetes were greatly reduced after the introduction of CGM, resulting in a significant reduction in costs. Data from clinical practice in Spain show that CGM is associated with improved blood glucose markers. Many studies analyzed these data during the COVID-19 pandemic and showed that CGM and analysis of glucometrics were highly useful during this time. New glucometrics and approaches to the analysis of data from CGM could help patients achieve better blood glucose control.

Diabetes Management Based on the Phenotype and Stage of the Disease: An Expert Proposal from the AGORA Diabetes Collaborative Group.

Diabetes is a complex and rapidly growing disease with heterogeneous clinical presentations. Recent advances in molecular and genetic technologies have led to the identification of various subtypes of diabetes. These advancements offer the potential for a more precise, individualized approach to treatment, known as precision medicine. Recognizing high-risk phenotypes and intervening early and intensively is crucial. A staging system for type 1 diabetes has been proposed and accepted globally. In this article, we will explore the different methods for categorizing and classifying type 2 diabetes (T2D) based on clinical characteristics, progression patterns, risk of complications, and the use of molecular techniques for patient grouping. We, as a team of experts, will also present an easy-to-follow treatment plan and guidance for non-specialists, particularly primary care physicians, that integrates the classification and staging of diabetes. This will help ensure that the most suitable therapy is applied to the different types of T2D at each stage of the disease's progression.

Metabolic and Clinical Outcomes in Type 1 Diabetes in the COVID-19 Pre- and Post-Vaccination Periods in Spain: The COVID-SED1 Study.

Aims: To evaluate the metabolic and clinical outcomes in the Spanish type 1 diabetes mellitus (T1D) population before and after COVID-19 vaccination. Methods: A retrospective observational study was carried out in Spanish public hospitals previously enrolled in the SED1 study. Adults and children with T1D were included and their clinical electronic records were reviewed. Clinical, laboratory, and glucometric parameters from continuous glucose monitoring (CGM) data corresponding to the periods before and after administering the first COVID-19 vaccination were analyzed. Results: A total of 26 centers and 228 patients participated in this new phase of the SED1 study and 187 were finally evaluable (mean age 37.5 ± 15.6 years, 56.7% women). Overall, 94.6% of the sample was vaccinated, and this percentage increased with higher levels of education (p-value = 0.027). In the pre- and post-vaccination periods, respectively, the number of patients with acute hyperglycemic decompensation was 6/161 (3.7%) and 7/161 (4.3%) (p = 1) and with acute hypoglycemic decompensation was 6/161 (3.7%) and 6/161 (3.7%) (p = 1). The HbA1c level was lower in the post-vaccination period(mean ± SD, mg/dL): pre-vaccination 7.4 ± 0.9; post-vaccination 7.2 ± 1.0, (-0.19; p-value = 0.0006). A total of 31.9% of patients (95% CI: 24.7-39.7) in the pre-vaccination period and 45.0% (IC95%: 37.1-53.1) in the post-vaccine period had HbA1c < 7% (p-value < 0.001). Glucometrics from CGM data also showed numerical improvements post-vaccination. Conclusions: The COVID-19 vaccination was highly accepted in the Spanish T1D population, with hesitancy about the COVID-19 vaccine being higher in those with lower educational levels. A mildly better glycemic control was observed in the post-vaccination period.

Ultrarapid Insulin Use Can Reduce Postprandial Hyperglycemia and Late Hypoglycemia, Even in Delayed Insulin Injections: A Connected Insulin Cap-Based Real-World Study.

Objectives: Reaching optimal postprandial glucose dynamics is a daily challenge for people with type 1 diabetes (T1D). This study aimed to analyze the postprandial hyperglycemic excursion (PHEs) and late postprandial hypoglycemia (LPH) risk according to prandial insulin time and type. Research Design and Methods: Real-world, retrospective study in T1D using multiple daily injections (MDI) analyzing 5 h of paired continuous glucose monitoring and insulin injections data collected from the connected cap Insulclock®. Meal events were identified using the rate of change detection methodology. Postprandial glucometrics and LPH (glucose <70 mg/dL 2-5 h after a meal) were evaluated according to insulin injection time and rapid (RI) or ultrarapid analog, Fiasp® (URI), use. Results: Meal glycemic excursions (n = 2488), RI: 1211, 48.7%; UR: 1277, 51.3%, in 82 people were analyzed according to injection time around the PHE: -45 to -15 min; -15 to 0 min; and 0 to +45 min. In 63% of the meals, insulin was injected after the PHE started. Lower PHE was observed with URI versus RI (glucose peak-baseline; mg/dL; mean ± standard deviation): 106.7 ± 35.2 versus 111.2 ± 40.3 (P = 0.003), particularly in 0/+45 injections: 111.6 ± 40.2 versus 118.1 ± 43.3; (P = 0.002). One third (29.1%) of participants added a second (correction) injection. The use of URI and avoiding a second injection were independently associated with less LPH risk, even in delayed injections (0/+45), (-36%, odds ratio [OR] 0.641; confidence interval [CI]: 0.462-0.909; P = 0.012) and -56% (OR 0.641; CI: 0.462-0.909 P = 0.038), respectively. Conclusions: URI analog use as prandial insulin reduces postprandial hyper- and hypoglycemia, even in delayed injections.

Nocturnal Glucose Profile According to Timing of Dinner Rapid Insulin and Basal and Rapid Insulin Type: An Insulclock® Connected Insulin Cap-Based Real-World Study.

BACKGROUND: A study to assess the glucose levels of people with type 1 diabetes (T1D) overnight, based on the insulin type and timing. METHODS: A real-world, retrospective study of T1D, using multiple daily insulin injections. Continuous glucose monitoring and insulin injection data were collected for ten hours after dinner using the Insulclock® connected cap. Meal events were identified using the ROC detection methodology. The timing of the rapid insulin, second injections, and the type of insulin analogs used, were evaluated. RESULTS: The nocturnal profiles (n = 775, 49 subjects) were analyzed. A higher glucose AUC of over 180 mg/dL was observed in subjects with delayed injections (number; %; mg/dL × h): -45-15 min (n = 136; 17.5%, 175.9 ± 271.0); -15-0 min (n = 231; 29.8%, 164.0 ± 2 37.1); 0 + 45 min (n = 408; 52.6%, 203.6 ± 260.9), (p = 0.049). The use of ultrarapid insulin (FiAsp®) (URI) vs. rapid insulin (RI) analogs was associated with less hypoglycemia events (7.1 vs. 13.6%; p = 0.005) and TBR70 (1.7 ± 6.9 vs. 4.6 ± 13.9%; p = 0.003). Users of glargine U300 vs. degludec had a higher TIR (70.7 vs. 58.5%) (adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n = 144, 18.6%) was associated with a higher number of hypoglycemia events (18.1 vs. 9.5%; p = 0.003), TBR70 (5.5 ± 14.2 vs. 3.0 ± 11.1%; p = 0.003), a glucose AUC of over 180 mg/dL (226.1 ± 257.8 vs. 178.0 ± 255.3 mg/dL × h; p = 0.001), and a lower TIR (56.0 ± 27.4 vs. 62.7 ± 29.6 mg/dL × h; p = 0.004). CONCLUSION: The dinner rapid insulin timing, insulin type, and the use of correction injections affect the nocturnal glucose profile in T1D.

Preventing alpelisib-related hyperglycaemia in HR+/HER2-/PIK3CA-mutated advanced breast cancer using metformin (METALLICA): a multicentre, open-label, single-arm, phase 2 trial.

Background: Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2-/PIK3CA-mutated advanced breast cancer (ABC). Methods: Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2-/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose <100 mg/dL [<5.6 mmol/L] and HbA1c <5.7%), and cohort B, prediabetes (fasting plasma glucose 100-140 mg/dL [5.6-7.8 mmol/L] and/or haemoglobin A1C [HbA1c] 5.7-6.4%). Participants were at least 18 years old, with Eastern Cooperative Oncology Group performance status of 0-1, and up to two prior lines of endocrine therapy (ET) for ABC. Alpelisib plus ET were administered in 28-day cycles after initiation of prophylactic metformin plus ET. Primary endpoint was the incidence of grade 3-4 hyperglycaemia over the first 8 weeks. Secondary endpoints included safety, progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR). The primary objective for cohort A and B is met with ≤7 (14.6%) and ≤4 (20%) patients with grade 3-4 hyperglycaemia over the first 8 weeks, respectively. Findings: 233 patients were screened, and 68 (20.2%) patients were enrolled in cohorts A (n = 48) and B (n = 20). Median follow-up was 7.8 months (IQR 1.4-19.6). Over the first 8 weeks, one (2.1%) of 48 patients in cohort A (95% CI: 0.5-11.1; P < 0.0001), and three (15.0%) of 20 patients in cohort B (95% CI: 5.6-37.8; P = 0.016) had grade 3-4 hyperglycaemia. Serious treatment-related adverse events occurred in seven patients (10.3%). The most common were rash (two [2.9%]), vomiting (two [2.9%]), and diarrhoea (two [2.9%]). Discontinuation of alpelisib caused by AEs was reported in nine patients (13.2%), none caused by hyperglycaemia. At data cutoff (15 June, 2022), no treatment-related deaths were observed. In the full analysis set, median PFS was 7.3 months (95% CI: 5.9-not reached), ORR was 20.6% (95% CI: 11.7-32.1%), and CBR was 52.9% (95% CI: 40.4-65.2). Interpretation: In HR+/HER2-/PIK3CA-mutated ABC, prophylactic metformin before alpelisib plus endocrine treatment has low incidence and severity of alpelicib-induced hyperglycaemia. Funding: Novartis Pharmaceuticals.

Connected Insulin Pens and Caps: An Expert's Recommendation from the Area of Diabetes of the Spanish Endocrinology and Nutrition Society (SEEN).

Undoubtedly, technological advances have revolutionised diabetes management in recent years. The development of advanced closed hybrid loop insulin pumps or continuous glucose monitoring (CGM) systems, among others, have increased the quality of life and improved glycaemic control of people with diabetes. However, only some patients have access to such technology, and only some want to use it. CGM has become much more widespread, but in terms of insulin delivery, most people with type 1 diabetes (T1D) and almost all people with type 2 diabetes (T2D) on insulin therapy are treated with multiple-dose insulin injections (MDI) rather than an insulin pump. For these patients, using connected insulin pens or caps has shown benefits in reducing missed insulin injections and promoting correct administration over time. In addition, using these devices improves the quality of life and user satisfaction. The integration of insulin injection and CGM data facilitates both users and the healthcare team to analyse glucose control and implement appropriate therapeutic changes, reducing therapeutic inertia. This expert's recommendation reviews the characteristics of the devices marketed or in the process of being marketed and their available scientific evidence. Finally, it suggests the profile of users and professionals who would benefit most, the barriers to its generalisation and the changes in the care model that implementing these devices can bring with it.

Efficacy of a Connected Insulin Pen Cap in People With Noncontrolled Type 1 Diabetes: A Multicenter Randomized Clinical Trial.

OBJECTIVE: To assess the efficacy of the insulin pen cap Insulclock on improving glycemic control, treatment adherence, and user satisfaction in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: This multicenter, open-label, randomized controlled trial comprised a 4-week run-in phase and a 6-week double-arm phase in which participants were randomly assigned into an active or masked mode. RESULTS: Fifty-five participants were evaluable (active group, n = 26, masked group, n = 29). The increase in time in range was higher in the active versus masked group (5.2% vs. -0.8%; P = 0.016). The active group showed a higher reduction in mean glucose, glucose management indicator, time above range, and high blood glucose index. On-time insulin doses increased in the active group and decreased in the masked group. CONCLUSIONS: Insulclock system use was associated with improved glycemic control, glycemic variability, hyperglycemia risk, and treatment adherence in people with uncontrolled type 1 diabetes.

Clinical Research on Type 2 Diabetes: A Promising and Multifaceted Landscape.

Type 2 diabetes constitutes an imposing epidemiological, economic, and scientific global challenge [...].

Are There Different Viewpoints About the Management of Type 2 Diabetes Mellitus and Comorbidities? A Multidisciplinary Spanish Qualitative Research.

INTRODUCTION: The aim of this study was to explore the vision of a large multidisciplinary group of physicians treating type 2 diabetes mellitus (T2DM) in Spain, with a special focus on controversial management aspects. The perceptions of primary care (PC) physicians and hospital care (HC) specialists were compared. METHODS: This was a mixed survey that included Delphi-like statements and opinion, attitude and behaviour (OAB) questions. The Delphi-like statements were assessed on the basis of the degree of agreement among respondents, and a descriptive analysis was performed on the answers to the OAB questions. RESULTS: A total of 296 participants responded to the first wave of the survey, of whom 293 responded to the second wave (211 from PC and 80 from HC, with two respondents for whom there were no data on specialty). A high degree of consensus (CNS ≥ 0.8) was obtained in all the statements. A proactive approach to detect prediabetes or T2DM in asymptomatic people was highly supported (80.4% of agreement). Introducing early treatment intensification was considered to favour the durability of glycaemic control and to delay the progression of the disease (80.4%). There was agreement on the statement that glycaemic variability constitutes a risk factor for chronic complications, although differences in the perceptions of HC physicians and PC specialists were identified (86.3 vs. 80.1%, respectively). More HC physicans than PC specialists considered comorbidities to affect the ability to self-care (95 vs. 82.9%, respectively). CONCLUSIONS: The survey revealed that there was a high, albeit not universal, degree of agreement amongst PC physicians and HC specialists in relation to prevention, screening and diagnosis of T2DM; early treatment intensification; dysglycaemias; and the management of patients with comorbidities. The statement on the management of patients with comorbidities elicited the highest difference between PC physicans and HC specialists. The results of this survey indicate that there is room for improvement in terms of implementing strategies in these areas.

Perceptions about the Management of Patients with DM2 and COVID-19 in the Hospital Care Setting.

BACKGROUND: COVID-19 entails a higher rate of complications in subjects with type 2 diabetes mellitus (T2DM). Likewise, COVID-19 infection can cause alterations in glucose metabolism that may lead to worse control. The aim of the study was to analyse the perceptions of a large group of Spanish physicians about the relationship between COVID-19 and T2DM, as well as the management, monitoring, and treatment of both diseases. METHODS: A cross-sectional multicenter national project was conducted based on a survey which included opinion, attitude, and behavior (OAB) questions. Physicians specialised in internal medicine or endocrinology, whose usual clinical practices included the management of T2DM, responded to the survey between March and April 2021. RESULTS: A total of 112 participants responded to the survey, from which 64.3% believed that COVID-19 entailed a higher risk of glycaemic decompensation irrespective of the presence of previously known T2DM. Obesity was considered a risk factor for poor control of T2DM by 57.7% and for a worse course of COVID-19 by 61.0%. Treatment intensification in not-on-target patients was considered by 57.1% in the presence of COVID-19 and by 73.2% in the absence of COVID-19. No participants considered the suspension of dipeptidyl peptidase 4 inhibitors (DPP-4i) in ambulatory patients, 85.7% declared that this therapeutic approach in hospitalized patients should be kept, and 88.4% supported the option of maintaining DPP-4i when corticosteroids were prescribed. CONCLUSION: The physicians involved in the management of T2DM and COVID-19 are aware of the bidirectional relationship between both conditions. However, the monitoring and therapeutic management of patients with T2DM who are infected by SARS-CoV-2 needs improvement through the following of the current recommendations and available evidence.

Non-Alcoholic Fatty Liver Disease and Risk of Macro- and Microvascular Complications in Patients with Type 2 Diabetes.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome. To date, NAFLD is the most frequent chronic liver disease seen day by day in clinical practice across most high-income countries, affecting nearly 25-30% of adults in the general population and up to 70% of patients with T2DM. Over the last few decades, it clearly emerged that NAFLD is a "multisystemic disease" and that the leading cause of death among patients with NAFLD is cardiovascular disease (CVD). Indeed, several observational studies and some meta-analyses have documented that NAFLD, especially its advanced forms, is strongly associated with fatal and non-fatal cardiovascular events, as well as with specific cardiac complications, including sub-clinical myocardial alteration and dysfunction, heart valve diseases and cardiac arrhythmias. Importantly, across various studies, these associations remained significant after adjustment for established cardiovascular risk factors and other confounders. Additionally, several observational studies and some meta-analyses have also reported that NAFLD is independently associated with specific microvascular conditions, such as chronic kidney disease and distal or autonomic neuropathy. Conversely, data regarding a potential association between NAFLD and retinopathy are scarce and often conflicting. This narrative review will describe the current evidence about the association between NAFLD and the risk of macro- and microvascular manifestations of CVD, especially in patients with T2DM. We will also briefly discuss the biological mechanisms underpinning the association between NAFLD and its advanced forms and macro- and microvascular CVD.

Patient Preferences for Pharmacological Diabetes Treatment Among People with Diabetes in Spain: A Discrete Choice Experiment.

INTRODUCTION: The aim of the project was to describe the preferences related to the medication attributes of people with diabetes mellitus (DM) treated in Spain. METHODS: The project was carried out in four different phases. In phase A, a Steering Committee defined and selected a total of 18 attributes for treating DM and grouped them into four categories: health outcomes, adverse events, treatment characteristics and cost of treatment. In phase B, a questionnaire according to a discrete choice experiment (DCE) methodology was developed. In phase C, the online DCE survey was sent to members of associations of people with DM from the Spanish Diabetes Federation (FEDE). Finally, in phase D, the results were discussed in a deliberative process. RESULTS: Of the 238 participants who completed the questionnaire (May-September 2020), 231 were included (mean age, 58 years; males, 62%). The DCE results showed that the best-valued category was health outcomes (39.67%), followed by adverse events (26.85%), treatment characteristics (21.70%) and treatment costs (11.77%). Ten of 18 attributes had a significant effect on participants' choice (p < 0.05) and the highest relative importance value: blood pressure reduction (12.82%), hypoglycaemia (12.77%), HbA1c level reduction (8.54%), cost of the medication (8.13%), needle/tablet size (7.20%), weight change (6.72%), risk of genitourinary infections (6.36%), gastrointestinal problems (5.82%), improved kidney function (5.53%) and administration route (5.41%). CONCLUSIONS: People with DM prefer a treatment that generates benefits in measurable health effects (reducing blood pressure and HbA1c level, while not risking hypoglycaemia) and a convenient route of administration. Considering the preferences of people with DM could generate better clinical results and therapeutic adherence, reducing morbidity, mortality and disease burden.

Usefulness of circulating EPAC1 as biomarkers of therapeutic response to GLP-1 receptor agonists.

AIMS: The response to Glucagon-like peptide-1 receptor agonists (GLP-1RAs) is highly varia-ble among patients. Thus, the identification of predictive biomarkers of therapeutic response to GLP-1 RA could help us to optimize the use of this class of drugs. GLP-1RAs increase exchange proteins directly activated by cAMP (EPAC). The aim of the present study was to assess whether the increase of EPAC1 after GLP-1RAs treatment could be a biomarker of clinical response. METHODS: After showing that GLP-1 (10 ng/mL) significantly increased the expression of EPAC1 in human endo-thelial vascular cells (HUVEC), a pilot clinical study was planned. For this purpose 49 patients with type 2 diabetes who started treatment with liraglutide were included. EPAC1 concentration was determined by ELISA before and at one month of liraglutide treatment. RESULTS: We found that serum concentration of EPAC1 increased significantly after treatment with liraglutide. Only in those patients in whom EPAC1 increased (64%), a significant decrease in HbA1c, LDL-C, body mass index (BMI), and waist circumference was shown. CONCLUSIONS: This pilot study suggests that the increase of circulating EPAC1 after GLP-1RAs treatment could be a useful biomarker to predict clinical GLP1-RAs response.